An orthogonal acceleration Time of Flight mass analyser in combination with an Electrospray ion source is known. It is known to measure the flight time of ions through a flight region of the orthogonal acceleration Time of Flight mass analyser. As the flight region is arranged perpendicular to the axis along which ions enter the orthogonal acceleration Time of Flight mass analyser, the time of flight measurements through the flight region are substantially unaffected by variations in the axial velocity of the ions. The decoupling of the axial velocity of the ions from the time of flight measurement results in higher mass measurement accuracy and a higher mass resolving power compared with axial Time of Flight mass analysers used in conjunction with pulsed ion sources such as, for example, Matrix Assisted Laser Desorption Ionisation (“MALDI”) ion sources.
One disadvantage, however, of using an orthogonal acceleration Time of Flight mass analyser is that the duty cycle for sampling a continuous ion beam in a MS mode of operation is relatively limited in that between 75% and 90% of the ions in the continuous ion beam are not extracted and hence are not orthogonally accelerated from the ion beam. Accordingly, these ions are lost to the system and this reduces the overall sensitivity of the orthogonal acceleration Time of Flight mass analyser and also results in relatively poor detection limits.
When a pulsed ion source, such as a Matrix Assisted Laser Desorption Ionisation (“MALDI”) ion source, is used in conjunction with an orthogonal acceleration Time of Flight mass analyser the ion loss tends to be even worse. The ions generated by a MALDI ion source will tend to have substantially the same ion energy irrespective of their mass to charge ratio and hence ions will tend to be emitted from the MALDI ion source at velocities which are inversely proportional to the square root of the mass to charge ratio of the ions. Accordingly, the ions generated from a MALDI ion source will tend to become spread out and will become temporally dispersed according to their mass to charge ratio as they exit the ion source. This temporal dispersion of ions according to their mass to charge ratio coupled with the limitation that the extraction or acceleration region of an orthogonal acceleration Time of Flight mass analyser can only sample a fraction of an ion beam entering the mass analyser at any one particular point in time results in only a portion of the total mass to charge ratio range of ions entering the orthogonal acceleration Time of Flight mass analyser being sampled in each extraction pulse.
A known approach which attempts to address this problem is to use a relatively low kinetic energy ion source (e.g. less than 100 eV) and to collisionally cool the ions. This process effectively transforms a pulse of ions into a pseudo-continuous beam of ions which is more suited for use with an orthogonal acceleration Time of Flight mass analyser. However, this approach is not completely effective since the pulse of ions is not transformed into a truly continuous beam. Collisional cooling of the ions can also cause problems since the collision gas may react with the analyte ions and form chemical adduct ions. Furthermore, the matrix used with MALDI ion sources tends to generate a significant amount of chemical noise which reduces the ion detection limit.
A known arrangement comprising a MALDI ion source, a collision or fragmentation cell and an orthogonal acceleration Time of Flight mass spectrometer has, however, been found to be advantageous when the mass spectrometer is operated in a MS/MS mode of operation. Ions accelerated with constant energy from the ion source will travel with velocities inversely proportional to the square root of their mass to charge ratio. In a MS mode of operation only ions having substantially the same mass to charge ratio or ions having a relatively narrow range of mass to charge ratios will arrive at the extraction or acceleration region of the orthogonal acceleration Time of Flight mass analyser at substantially the same time and hence will be pulsed into the flight region of the mass analyser. In contrast in a MS/MS mode of operation fragment ions formed, for example, in a collision cell downstream of the ion source and upstream of the orthogonal acceleration Time of Flight extraction or acceleration region will have substantially the same velocity as that of their corresponding parent ions. Accordingly, in a MS/MS mode of operation all the fragment ions of a particular parent ion will arrive at the extraction or acceleration region of an orthogonal acceleration Time of Flight mass analyser together with any corresponding unfragmented parent ions at substantially the same time. The time at which the fragment ions will arrive at the extraction or acceleration region will also be substantially the same time that the corresponding parent ion would have arrived at the extraction or acceleration region if the corresponding parent ion had not fragmented. Therefore, the mass spectra recorded when the mass spectrometer is operated in a MS/MS mode of operation will advantageously include just a narrow range of parent ions and all the fragment ions from those particular parent ions.
It is desired to provide an improved mass spectrometer and in particular to provide a mass spectrometer which enables a pulsed ion source to be operated efficiently in conjunction with a Time of Flight mass analyser in a MS mode of operation.
It is also desired to provide a mass spectrometer which has a high duty cycle in a MS mode of operation.